Bucinnazine

Bucinnazine
Legal status
Legal status	UK: Under Psychoactive Substances Act;
Identifiers
	IUPAC name 1-[4-[(E)-3-Phenylprop-2-enyl]piperazin-1-yl]butan-1-one;
CAS Number	17719-89-0 ;
PubChem CID	6005081;
ChemSpider	4777510;
UNII	J735KL8O54;
Chemical and physical data
Formula	C17H24N2O
Molar mass	272.392 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CCCC(=O)N1CCN(CC1)C/C=C/C2=CC=CC=C2;
	InChI InChI=1S/C17H24N2O/c1-2-7-17(20)19-14-12-18(13-15-19)11-6-10-16-8-4-3-5-9-16/h3-6,8-10H,2,7,11-15H2,1H3/b10-6+; Key:ZQBMUHABRSEAIK-UXBLZVDNSA-N;

AP-237 (also known as Bucinnazine and 1-butyryl-4-cinnamylpiperazine) is an opioid analgesic drug that was widely used in China to treat pain in cancer patients as of 1986.^[1] It is one of the most potent compound among a series of analgesic acyl piperazines compounds first synthesized and reported in Japan in the 1970s.^[2]^[3]^[4] AP-237 has analgesic potency comparable to that of morphine but with a relatively higher therapeutic index. The drug were initially claimed to be a non-narcotic analgesic. However, subsequent studies have shown AP-237 and similar acyl piperazines to be potent and selective agonists of μ-opioid receptor (MOR) with relatively low affinity for the δ-opioid receptor and the κ-opioid receptor.^[5] In accordance with these studies, results from the intravenous self-administration experiments in rats showed that AP-237 has a marked reinforcing effect with tolerance and dependence quickly developing.^[1] In addition, the morphine antagonist naloxone reverses the effect of AP-237 and precipitates withdrawal symptoms in AP-237 treated rats further indicating a mechanism of analgesia mediated via selective agonist activity at μ-opioid receptors.

References

^ ^a ^b Qing T, Zhi-Ji C, and Wei-Ping W. Experimental Study on the Dependence-Producing Properties of Qiang Tong Ding (AP-237). Chin. J. Clin. Pharmacol. 1986 -02, http://en.cnki.com.cn/Article_en/CJFDTotal-GLYZ198602003.htm
^ Nishimura N, Kiuchi M, Kanetake Y, Takahashi T. Clinical exaluation of a new analgesic agent Ap-237. Masui. 1970 Jun;19(6):653-6. Japanese. No abstract available. PMID 4916908
^ Carrano RA, Kimura KK, McCurdy DH. Analgesic and tolerance studies with AP-237, a new analgesic. Arch Int Pharmacodyn Ther. 1975 Jan;213(1):41-57. PMID 1156018
^ Carrano RA, Kimura KK, Landes RC, McCurdy DH. General pharmacology of a new analgesic-AP-237. Arch Int Pharmacodyn Ther. 1975 Jan;213(1):28-40. PMID 1156016
^ Barlocco, D; Cignarella, G; Greco, G; Novellino, E (1993). "Computer-aided structure-affinity relationships in a set of piperazine and 3,8-diazabicyclo3.2.1octane derivatives binding to the mu-opioid receptor". Journal of Computer-Aided Molecular Design. 7 (5): 557–71. doi:10.1007/bf00124362. PMID 8294946

[Qing1986-1] Qing T, Zhi-Ji C, and Wei-Ping W. Experimental Study on the Dependence-Producing Properties of Qiang Tong Ding (AP-237). Chin. J. Clin. Pharmacol. 1986 -02, http://en.cnki.com.cn/Article_en/CJFDTotal-GLYZ198602003.htm

[2] Nishimura N, Kiuchi M, Kanetake Y, Takahashi T. Clinical exaluation of a new analgesic agent Ap-237. Masui. 1970 Jun;19(6):653-6. Japanese. No abstract available. PMID 4916908

[3] Carrano RA, Kimura KK, McCurdy DH. Analgesic and tolerance studies with AP-237, a new analgesic. Arch Int Pharmacodyn Ther. 1975 Jan;213(1):41-57. PMID 1156018

[4] Carrano RA, Kimura KK, Landes RC, McCurdy DH. General pharmacology of a new analgesic-AP-237. Arch Int Pharmacodyn Ther. 1975 Jan;213(1):28-40. PMID 1156016

[5] Barlocco, D; Cignarella, G; Greco, G; Novellino, E (1993). "Computer-aided structure-affinity relationships in a set of piperazine and 3,8-diazabicyclo3.2.1octane derivatives binding to the mu-opioid receptor". Journal of Computer-Aided Molecular Design. 7 (5): 557–71. doi:10.1007/bf00124362. PMID 8294946

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